Patents Assigned to Boehringer Ingelheim (Canada) Ltd.
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Publication number: 20030162169Abstract: The present invention concerns the development of a cell-based assay system having improved sensitivity to HCV NS3 protease activity when compared to known assays, which is useful for screening test compounds capable of modulating (particularly inhibiting) HCV NS3 protease activity. This system provides a first construct comprising a transactivator domain joined downstream of the NS3-5 domains of HCV under the control of a non-cytopathic viral promoter system. A second construct is also provided that comprises a reporter gene under the control of an operator sensitive to the binding of the transactivator. The NS3-5 domains encodes the NS3 polyprotein which comprises: the NS3 protease, followed by the NS4A co-factor, the NS4B and NS5A proteins (including any derivative, variant or fragment thereof), terminated by the NS5B protein (including any derivative, variant or fragment thereof) sufficient to constitute a NS5A/5B cleavage site.Type: ApplicationFiled: December 23, 2002Publication date: August 28, 2003Applicant: Boehringer Ingelheim (Canada) Ltd.Inventors: Charles Pellerin, Daniel Lamarre
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Patent number: 6608027Abstract: The present invention covers macrocyclic compounds of formula I active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus. wherein W, R21, R22, R3, R4, D and A are as defined herein, or a pharmaceutically acceptable salts or ester thereof.Type: GrantFiled: January 16, 2001Date of Patent: August 19, 2003Assignee: Boehringer Ingelheim (Canada) LtdInventors: Youla S. Tsantrizos, Dale R. Cameron, Anne-Marie Faucher, Elise Ghiro, Nathalie Goudreau, Teddy Halmos, Montse Llinas-Brunet
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Publication number: 20030148348Abstract: A unique HCV RNA molecule is provided having an enhanced efficiency of establishing cell culture replication. Novel adaptive mutations have been identified within the HCV non-structural region that improves the efficiency of establishing persistently replicating HCV RNA in cell culture. This self-replicating polynucleotide molecule contains, contrary to all previous reports, a 5′-NTR that can be either an A as an alternative to the G already disclosed and therefore provides an alternative to existing systems comprising a self-replicating HCV RNA molecule. The G->A mutation gives rise to HCV RNA molecules that, in conjunction with mutations in the HCV non-structural region, such as the G(2042)C/R mutations, possess greater efficiency of transduction and/or replication. These RNA molecules when transfected in a cell line are useful for evaluating potential inhibitors of HCV replication.Type: ApplicationFiled: December 4, 2002Publication date: August 7, 2003Applicant: Boehringer Ingelheim (Canada) Ltd.Inventors: George Kukolj, Arnim Pause
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Patent number: 6596924Abstract: The present invention relates to a graft animal model for propagating papilloma virus and for evaluating and testing candidate therapeutic agents against papilloma virus. The animal model comprises, a recipient animal engrafted with injured skin graft infected with a host-specific papilloma virus (PV). The grafted skin, having demonstrable papillomas supports the propagation of its host-specific PV. The invention particularly relates to a xenograft animal model for hosting and propagating human papillomavirus (HPV), thereby providing a means for generating infectious and passaging HPV suspensions, and for screening candidate therapeutic agents against HPV. The invention additionally relates to a novel method for generating the xenograft human animal model.Type: GrantFiled: December 17, 1999Date of Patent: July 22, 2003Assignee: Boehringer Ingelheim (Canada) Ltd.Inventor: Duan Jianmin
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Publication number: 20030108862Abstract: A method for identifying compounds binding to HCV polymerase comprising the steps of:contacting said HCV polymerase or an analog thereof with a probe formula I: 1Type: ApplicationFiled: August 2, 2002Publication date: June 12, 2003Applicant: Boehringer Ingelheim (Canada) Ltd.Inventors: George Kukolj, Pierre Louis Beaulieu, Ginette McKercher
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Publication number: 20030087379Abstract: A method for measuring heterodimerization of HIV RT, which comprises the steps of:Type: ApplicationFiled: July 25, 2002Publication date: May 8, 2003Applicant: Boehringer Ingelheim (Canada) Ltd.Inventors: Nicolas Sluis-Cremer, Michael Parniak, Alex Pelletier
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Publication number: 20030082769Abstract: A crystallizable composition, comprising an PV E2 TAD-like polypeptide of SEQ ID NO.2 complexed with an inhibitor L. The invention also provides a method for producing the crystallized HPV E2 TAD-inhibitor complex (HPV E2 TAD-L) comprising: a) mixing purified HPV E2 TAD, contained in a purfication buffer, with solublized inhibitor L to generate a complex solution containing the HPV E2 TAD-L complex; and b) crystallizing the complex from a) in a crystallization buffer. The invention also provides a method for producing crystallized apo HPV E2 TAD, comprising: a) mixing apo HPV E2 TAD, contained in a purification buffer, with a crystallization buffer. X-ray crystal structure coordinates the HPV E2 TAD-L complex, are also provided, which define an inhibitor binding pocket. The inhibitor binding pocket is useful for screening potential small molecule inhibitors that bind to the pocket.Type: ApplicationFiled: July 11, 2002Publication date: May 1, 2003Applicant: Boehringer Ingelheim (Canada) Ltd.Inventors: Dale R. Cameron, Jacques Archambault, Christiane Yoakim, Peter White, Yong Wang
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Patent number: 6534523Abstract: Racemates, diastereoisomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl oType: GrantFiled: March 5, 2002Date of Patent: March 18, 2003Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Montse Llinas-Brunet, Murray D. Bailey, Dale R. Cameron, Elise Ghiro, Nathalie Goudreau, Marc-Andre Poupart, Jean Rancourt, Youla S. Tsantrizos, Anne-Marie Faucher, Teddy Halmos, Dominik M. Wernic
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Patent number: 6492181Abstract: The present invention uses the principle that phosphomolybdate binds to hydrophobic surfaces to isolate the phosphomolybdate complex from other phosphate-containing molecules and further uses the SPA concept to bring a radiolabeled phosphomolybdate complex in close contact with a scintillant for measurement by scintillation counting. Generally, the present invention provides an assay for detecting and measuring the amount of orthophosphate (Pi) in an aqueous reaction mixture, wherein the amount of Pi released is separated from the reaction mixture by: adding a solution of molybdate to the reaction mixture to form a phosphomolybdate complex; and contacting the phosphomolybdate complex with a hydrophobic surface, wherein the surface is capable of being separated from the aqueous reaction mixture to allow measurement of the Pi. Particularly, this invention provides an assay for measuring the ATPase activity of enzymes, more particularly, the HPV E1 helicase.Type: GrantFiled: June 16, 2000Date of Patent: December 10, 2002Assignee: Boehringer Ingelheim (Canada) Ltd.Inventor: Peter White
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Patent number: 6479508Abstract: A compound of the formula I: wherein: X is CH or N; Y is O or S; Z is OH, NH2, NMeR3, NHR3; OR3 or 5- or 6-membered heterocycle, having 1 to 4 heteroatoms selected from O, N and S, said heterocycle being optionally substituted with from 1 to 4 substituents; A is N, COR7 or CR5, wherein R5 is H, halogen, or (C1-6) alkyl and R7 is H or (C1-6 alkyl), with the proviso that X and A are not both N; R6 is H, halogen, (C1-6 alkyl) or OR7, wherein R7 is H or (C1-6 alkyl); R1 is selected from the group consisting of 5- or 6-membered heterocycle having 1 to 4 heteroatoms selected from O, N, and S, phenyl, phenyl(C1-3)alkyl, (C2-6)alkenyl, phenyl(C2-6)alkenyl, (C3-6)cycloalkyl, (C1-6)alkyl, CF3, 9- or 10-membered heterobicycle having 1 to 4 heteroatoms selected from O, N and S, wherein said heterocycle, phenyl, phenyl(C2-6)alkenyl and phenyl(C1-3)alkyl), alkenyl , cycloalkyl, (C1-6)alkyl, and heterobicycle are all optionally substituted with from 1 to 4 substituents; R2 is selected from (C1-6)alkyl,Type: GrantFiled: November 27, 2001Date of Patent: November 12, 2002Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Pierre Louis Beaulieu, Gulrez Fazal, James Gillard, George Kukolj, Volkhard Austel
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Patent number: 6458959Abstract: This invention relates to methods for inhibiting herpes replication and for treating herpes infection in a mammal by inhibiting the herpes helicase-primase enzyme complex. This invention also relates to thiazolyphenyl derivatives that inhibit the herpes helicase-primase and to pharmaceutical compositions comprising the thiazolylphenyl derivatives, to methods of using and methods of producing the thiazolylphenyl derivatives.Type: GrantFiled: October 10, 2000Date of Patent: October 1, 2002Assignees: Boehringer Ingelheim Pharmaceuticals, Inc., Boehringer Ingelheim (Canada) Ltd.Inventors: James J. Crute, Anne-Marie Faucher, Christine A. Grygon, Karl D. Hargrave, Bruno Simoneau, Bounkham Thavonekham
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Patent number: 6448281Abstract: A compound of the formula I: wherein: X is CH or N; Y is O or S; Z is OH, NH2, NMeR3, NHR3; OR3 or 5- or 6-membered heterocycle, having 1 to 4 heteroatoms selected from O, N and S, said heterocycle being optionally substituted with from 1 to 4 substituents; A is N, COR7 or CR5, wherein R5 is H, halogen, or (C1-6) alkyl and R7 is H or (C1-6 alkyl), with the proviso that X and A are not both N; R6 is H, halogen, (C1-6 alkyl) or OR7, wherein R7 is H or (C1-6 alkyl); R1 is selected from the group consisting of 5- or 6-membered heterocycle having 1 to 4 heteroatoms selected from O, N, and S, phenyl, phenyl(C1-3)alkyl, (C2-6)alkenyl, phenyl(C2-6)alkenyl, (C3-6)cycloalkyl, (C1-6)alkyl, CF3, 9- or 10-membered heterobicycle having 1 to 4 heteroatoms selected from O, N and S, wherein said heterocycle, phenyl, phenyl(C2-6)alkenyl and phenyl(C1-3)alkyl), alkenyl, cycloalkyl, (C1-6)alkyl, and heterobicycle are all optionally substituted with from 1 to 4 substituents; R2 is selected from (C1-6)alkyl, (CType: GrantFiled: July 3, 2001Date of Patent: September 10, 2002Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Pierre Louis Beaulieu, Gulrez Fazal, James Gillard, George Kukolj, Volkhard Austel
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Patent number: 6420359Abstract: Provided are compounds of the general formula I: wherein R2 is selected from the group consisting of H, F, Cl, (C1-4) alkyl, (C3-4) cycloalkyl and CF3; R4 is H or Me; R5 is H, Me or Et, with the proviso that R4 and R5 are not both Me, and if R4 is Me then R5 cannot be Et; R11 is Et, cyclopropyl, propyl, isopropyl, or isobutyl; and Q is selected from the group consisting of: and pharmaceutically acceptable salts thereof, as inhibitors of HIV reverse transcriptase, wild-type and several mutant strains.Type: GrantFiled: June 12, 2001Date of Patent: July 16, 2002Assignee: Boehringer Ingelheim (Canada) Ltd.Inventor: Bruno Simoneau
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Patent number: 6420380Abstract: Racemates, diastereoisomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl oType: GrantFiled: April 6, 2001Date of Patent: July 16, 2002Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Montse Llinas-Brunet, Murray D. Bailey, Dale R. Cameron, Ellse Ghiro, Nathalie Goudreau, Marc-Andre Poupart, Jean Rancourt, Youla S. Tsantrizos, Anne-Marie Faucher, Teddy Halmos, Dominik M. Wernic
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Patent number: 6410531Abstract: Racemates, diastereoisomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl oType: GrantFiled: May 4, 2001Date of Patent: June 25, 2002Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Montse Llinas-Brunet, Murray D. Bailey, Dale R. Cameron, Elise Ghiro, Nathalie Goudreau, Marc-Andre Poupart, Jean Rancourt, Youla S. Tsantrizos, Anne-Marie Faucher, Teddy Halmos, Dominik M. Wernic
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Patent number: 6348477Abstract: This invention relates to methods for inhibiting herpes replication and for treating herpes infection in a mammal by inhibiting the herpes helicase-primase enzyme complex. This invention also relates to thiazolyphenyl derivatives that inhibit the herpes helicase-primase and to pharmaceutical compositions comprising the thiazolylphenyl derivatives, to methods of using and methods of producing the thiazolylphenyl derivatives.Type: GrantFiled: December 8, 1999Date of Patent: February 19, 2002Assignees: Boehringer Ingelheim(Canada) Ltd., Boehringer Ingelheim Pharmaceuticals, Inc.Inventors: James J. Crute, Anne-Marie Faucher, Christine A. Grygon, Karl D. Hargrave, Bruno Simoneau, Bounkham Thavonekham
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Patent number: 6329417Abstract: Racemates, diastereolsomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl orType: GrantFiled: November 1, 2000Date of Patent: December 11, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Montse Llinas-Brunet, Murray D. Bailey, Dale R. Cameron, Elise Ghiro, Nathalie Goudreau, Marc-Andre Poupart, Jean Rancourt, Youla S. Tsantrizos, Anne-Marie Faucher, Teddy Halmos, Dominik M. Wernic
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Patent number: 6329379Abstract: Racemates, diastereoisomers and optical isomers of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl of formula R4—O—C(O)—; an amide of formula R4—N(R5)—C(O)—; a thioamide of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl oType: GrantFiled: September 29, 2000Date of Patent: December 11, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Montse Llinas-Brunet, Murray D. Bailey, Dale R. Cameron, Elise Ghiro, Nathalie Goudreau, Marc-Andre Poupart, Jean Rancourt, Youla S. Tsantrizos, Anne-Marie Faucher, Teddy Halmos, Dominik M. Wernic
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Patent number: 6323202Abstract: The invention provides compounds of the formula 1 that are active against the HSV primase enzyme: wherein R1 is hydroxy or amino; R2 is hydrogen, halo, (C1-4)alkyl or (C1-4)alkoxy; R3 is hydrogen, halo, (C1-4)alkyl, (C1-4)alkoxy, amino or azido; R4 has the same significance as R2; R5 is hydrogen or (C1-4)alkyl; and R is (C1-7)alkyl, (C3-6)cycloalkyl, {phenyl(C1-7)alkyl}, {phenyl(C1-7)alkoxy}, {{(monocyclic heterocyclo)-{(C1-7)alkoxy}}, CH(W)C(O){O-(C1-4)alkyl} wherein W is hydrogen or (C1-7)alkyl, or wherein Y is hydrogen or (C1-7)alkyl, and Z is (C1-7)alkyl, (C3-6) cycloalkyl, {(C3-6)cycloalkyl}- {(C1-7)alkyl}, phenyl(C1-7)alkyl or {{(monocyclic heterocyclo)-{(C1-7)alkyl}}, or Y and Z together with the nitrogen atom to which they are attached represent, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl or 1-(4-methylpiperazinyl); with the provisos that (1) when R is CH(WType: GrantFiled: March 24, 2000Date of Patent: November 27, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Bruno Simoneau, Michele Liuzzi, Anton Mentrup
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Patent number: 6323180Abstract: A racemate, diastereoisomer and optical isomer of a compound of formula (I): wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which may be optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4—C(O)—; a carboxyl derivative of formula R4—O—C(O)—; an amide derivative of formula R4—N(R5)—C(O)—; a thioamide derivative of formula R4—N(R5)—C(S)—; or a sulfonyl of formula R4—SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C1-8 alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2—R20, NH—R20, O—R20 or S—R20, wherein R20 is a satuType: GrantFiled: August 5, 1999Date of Patent: November 27, 2001Assignee: Boehringer Ingelheim (Canada) LtdInventors: Montse Llinas-Brunet, Murray D. Bailey, Dale Cameron, Elise Ghiro, Nathalie Goudreau, Marc-AndrĂ© Poupart, Jean Rancourt, Youla S. Tsantrizos, Anne-Marie Faucher, Teddy Halmos, Dominik M. Wernic, Bruno Simoneau